Is ATM p.Ile34Phe (c.100A>T) pathogenic?

ATM p.Ile34Phe (c.100A>T) is classified Uncertain significance in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-08). AlphaMissense: ambiguous (0.4826); Absent from gnomAD v4.1.

How common is ATM p.Ile34Phe (c.100A>T) in the general population?

ATM p.Ile34Phe (c.100A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATM p.Ile34Phe (c.100A>T)?

AlphaMissense predicts ambiguous (score 0.4826) — an in-silico prediction, not a clinical call.

ATM p.Ile34Phe

c.100A>T · rs1555054094 · VCV633060

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4826 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4826	ambiguous
REVEL	0.173	moderately benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATM
Protein: p.Ile34Phe
Coding: c.100A>T
MANE Select: NM_000051
dbSNP: rs1555054094
Type: single nucleotide variant
Location: chr11:108227803 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

Full ATM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATM p.Ile34Val Conflicting classifications of pathogenicity ★ ⚠ same residue
ATM p.Ile34= Likely benign ★ same residue
ATM c.1607+1G>T Pathogenic ★★★ same type
ATM c.2251-2A>T Pathogenic ★★★ same type
ATM c.2251-4A>G Likely pathogenic ★★★ same type
ATM c.2466+5G>C Likely pathogenic ★★★ same type
ATM c.3078-1G>A Pathogenic ★★★ same type
ATM c.332-1G>A Pathogenic ★★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/atm-p-ile34phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown